Patients with recurrent acute myocardial infarction (AMI), who represent ≤35% of hospitalized patients with AMI, are at an increased risk of complications and death. Our study purpose was to compare the treatment and outcome of patients hospitalized with recurrent acute ST-segment elevation myocardial infarction (STEMI) from 1998 to 2006 with those of patients with a first STEMI. We performed 5 biennial nationwide 2-month surveys during 1998 to 2006, collecting data prospectively from all patients hospitalized for AMI or acute coronary syndrome in all 25 coronary care units in Israel. The present cohort included 4,543 patients with STEMI, 3,679 (76%) with first and 864 (24%) with recurrent STEMI. The patients with recurrent STEMI were older (66 ± 13 vs 62 ± 13 years), had greater rates of diabetes, hypertension, and previous angina, had a worse Killip class on admission, and experienced more in-hospital complications. The all-cause hospital crude mortality rate was 8.1% in patients with recurrent STEMI versus 5.5% in those with a first STEMI (adjusted odds ratio 1.71 95% confidence interval 1.19 to 2.44), and the 1-year mortality rate was 18.9% versus 10.9%, respectively (hazard ratio 1.85, 95% confidence interval 1.41 to 2.43). From 1998 to 2006, an insignificant trend toward a 1-year mortality reduction among patients with recurrent STEMI was seen and those with a first STEMI had a significant mortality decrease. In conclusion, patients admitted for recurrent STEMI have worse in-hospital and 1-year outcomes that did not improve during the study period. An improved therapeutic approach is needed for these high-risk patients.
Patients with recurrent acute myocardial infarction (AMI), who represent ≤35% of hospitalized patients with AMI, are at an increased risk of complications and death. Of patients with ST-segment elevation MI (STEMI), they represent 29% to 47% of those with AMI/acute coronary syndromes (ACS) in large databases, depending on their age and the type of surveillance. Because STEMI and non-STEMI differ in management, the present study concentrated only on patients with STEMI. Despite the high prevalence and poor prognosis of patients with recurrent STEMI, only a few reports have been published on changes in the incidence or outcome of this important subgroup during the past decade. In contrast, improvement in the outcome of first STEMI has been documented in many studies. The purpose of the present study was to report the incidence, management, and outcome of patients with recurrent STEMI and to compare them with those with first STEMI hospitalized from 1998 to 2006 in all coronary care units (CCUs) in Israel.
Methods
Five biennial, prospective, nationwide, 2-month surveys were conducted in all 25 operating CCUs in Israel, collecting data prospectively for all patients with AMI/ACS hospitalized during January to February 1998, February to March 2000, February to March 2002, February to March 2004, and March to April 2006. The details of these surveys, called Acute Coronary Syndrome Israeli Survey (ACSIS), have been previously described.
Data on patient characteristics, in-hospital course, and management during their CCU hospitalization were collected and recorded on prespecified structured forms. The diagnoses of MI, hypertension, diabetes mellitus, and dyslipidemia were determined by the local survey team. We did not follow-up our patients clinically after discharge and, therefore, had no data about additional hospitalizations, compliance with medications, or additional interventions. Recurrent STEMI was defined as STEMI, diagnosed using standard criteria, preceded by ≥1 MI (STEMI or non-STEMI) before the index hospitalization. Mortality was assessed for 99% of patients by matching their identification numbers with the Israeli National Population Registry. We could not retrieve the cause of death.
All analyses were performed using SAS software, version 8.2 (SAS Institute, Cary, North Carolina). The continuous variables are reported as the mean ± SD. The chi-square test and analysis of variance were used to determine the significance of the differences between the proportions and mean values, respectively. Survival curves were constructed using the Kaplan-Meier method. The significance of difference between survival curves was assessed using the log-rank test (SAS LIFETEST procedure). Multivariate stepwise logistic regression analysis (SAS LOGISTIC procedure) was performed to identify variables associated with in-hospital and 30-day mortality and to compare the mortality in patients with recurrent versus first STEMI in terms of the odds ratio with 95% confidence intervals. Multivariate analyses of the 6-month and 1-year mortality were done, using the Cox proportional hazards model, and results are reported as the hazards ratio and 95% confidence intervals. We included in the models a broad range of characteristics shown to be statistically significant (p <0.10) on univariate analysis. A test based on a different time-dependent covariate was used to assess the proportionality of hazards. Missing values were included in the models as separate categories. When comparing periods, the earlier period (1998 to 2000), was used as the reference and, when comparing recurrent versus the first STEMI patient group, the latter was used as the reference group (odds ratio/hazards ratio = 1).
Results
During the survey period, 7,097 patients with AMI (STEMI and non-STEMI) were hospitalized. Of the 7.097 patients, 5,394 (76%) had a first AMI and 1,703 (24%) a recurrent AMI. The first AMI population included 3,679 patients (68%) with STEMI and the recurrent AMI group included only 864 patients (51%) with STEMI. The patients with STEMI constituted the present study population. The percentage of admissions for STEMI of the total AMI admissions decreased significantly in both groups during the study period from 62% in 1998 to 37% in 2006 in the recurrent STEMI group and from 78% to 59% in the first STEMI group.
The patients with recurrent STEMI were older, more often men, had more risk factors for coronary artery disease, and had a higher Killip class on admission than the patients with a first STEMI ( Table 1 ). The proportion of patients with hypertension, dyslipidemia, and previous percutaneous coronary intervention (PCI) increased during the study period in both groups.
| Variable | STEMI Type | p Value Recurrent vs first STEMI | p Value for Trend During Study Period | ||
|---|---|---|---|---|---|
| Recurrent (n = 864) | First (n = 3,679) | Recurrent STEMI (n = 864) | First STEMI (n = 3,679) | ||
| Mean age (years) | 65.4 ± 12.6 | 61.9 ± 13.1 | <0.0001 | <0.58 | <0.04 |
| Women | 20.6% | 24.2% | <0.03 | <0.29 | <0.03 |
| Diabetes | 37.2% | 25.7% | <0.0001 | <0.39 | <0.32 |
| Hypertension | 54.4% | 42.1% | <0.0001 | <0.0001 | <0.006 |
| Dyslipidemia | 57.6% | 40.1% | <0.0001 | <0.0001 | <0.0001 |
| Current smokers | 38.3% | 42.3% | <0.04 | <0.09 | <0.0005 |
| Previous stroke | 11.5% | 6.0% | <0.0001 | <0.02 | <0.43 |
| Previous angina pectoris | 42.2% | 19.5% | <0.0001 | <0.94 | <0.0001 |
| Previous percutaneous coronary intervention | 41.4% | 3.8% | <0.0001 | <0.0001 | <0.0002 |
| Previous coronary artery bypass grafting | 10.8% | 1.3% | <0.0001 | <0.04 | <0.98 |
| Anterior infarct | 41.1% | 47.1% | <0.002 | <0.41 | <0.03 |
| Killip class II or greater | 28.1% | 17.9% | <0.0001 | <0.21 | <0.03 |
| Maximal creatine phosphokinase (IU) | 1,436 | 1,696 | <0.005 | <0.84 | <0.04 |
The interval from arrival to reperfusion therapy was similar for both groups. The patients with recurrent STEMI patients less frequently underwent primary reperfusion, were referred less for coronary angiography, and underwent fewer PCIs procedures than the patients with first STEMI ( Table 2 and Appendix Table IIA ). Their medical management less often included glycoprotein IIb/IIIa antagonists but more often included digoxin and nitrates. During their hospitalization, patients with recurrent STEMI experienced pulmonary congestion/edema, cardiogenic shock, and asystole more frequently than their first STEMI counterparts.
| Variable | Recurrent STEMI (n = 864) | First STEMI (n = 3,679) | p Value | ||
|---|---|---|---|---|---|
| Recurrent vs first | Trend for Recurrent | Trend for First | |||
| Reperfusion | |||||
| Median door to reperfusion interval (min) | 66 | 62 | 0.22 | 0.21 | 0.17 |
| Primary reperfusion | 55.2% | 62.7% | 0.0001 | 0.98 | 0.07 |
| Thrombolysis | 31.3% | 35.1% | 0.03 | 0.0001 | 0.0001 |
| Percutaneous coronary intervention | |||||
| Primary | 24.5% | 27.8% | 0.06 | 0.0001 | 0.0001 |
| Not primary | 25.5% | 29.7% | 0.02 | 0.58 | 0.05 |
| Coronary bypass | 5.6% | 4.0% | 0.04 | 0.07 | 0.70 |
| Complications | |||||
| Asystole | 4.5% | 3.0% | 0.02 | 0.34 | 0.93 |
| Cardiogenic shock | 9.0% | 5.4% | 0.0001 | 0.39 | 0.45 |
| Pulmonary congestion/edema | 24.9% | 17.5% | 0.0001 | 0.07 | 0.10 |
| Stroke/transient ischemic attack | 1.5% | 1.0% | 0.21 | 0.66 | 0.69 |
| Ventricular tachycardia/ventricular fibrillation | 11.7% | 11.6% | 0.93 | 0.35 | 0.02 |
| Major bleeding | 1.5% | 0.9% | 0.64 | 0.13 | 0.17 |
| Second- or third-degree atrioventricular block | 5.9% | 5.0% | 0.28 | 0.02 | 0.0003 |
| Pacemaker | 5.0% | 4.0% | 0.19 | 0.002 | 0.35 |
| Medication (in hospital) | |||||
| Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers | 68.9% | 66.1% | NS | 0.0001 | 0.0001 |
| Glycoprotein IIb/IIIa | 29.1% | 34.7% | 0.002 | 0.0001 | 0.0001 |
| Medication (at discharge) | |||||
| Angiotensin-converting enzyme inhibitors | 66.4% | 62.5 | 0.11 | 0.09 | 0.0001 |
| Aspirin | 94.0% | 94.4% | 0.75 | 0.40 | 0.0001 |
| Ticlopidine/clopidogrel | 48.9% | 55.0% | 0.02 | 0.0001 | 0.0001 |
| β Blockers | 75.7% | 76.7% | 0.56 | 0.0001 | 0.0001 |
| Calcium channel blockers | 7.9% | 7.6% | 0.93 | 0.84 | 0.0008 |
| Digoxin | 4.5 | 2.0% | 0.0001 | 0.13 | 0.26 |
| Lipid-lowering drugs | 68.1% | 65.2% | 0.12 | 0.0001 | 0.0001 |
| Nitrates | 34.0% | 25.2% | 0.0001 | 0.0001 | 0.0001 |
Throughout the study period, the rates of coronary angiography, primary and overall PCI and stent implantation increased and the use of thrombolysis decreased in both cohorts. Significant changes in medical therapy were also noted in both groups. An increase occurred in the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, glycoprotein IIb/IIIa antagonists, β blockers, thienopyridines, and lipid-lowering drugs, and the use of nitrates decreased. The rate of pacemaker implantation increased only among patients with recurrent STEMI.
During the first year after their acute event, patients with recurrent STEMI had significantly greater crude and covariate adjusted all-cause mortality rates than the patients with a first STEMI ( Tables 3 to 6 and Figures 1 and 2 ). During the study period, patients with recurrent STEMI had an insignificant decrease in the 30-day, 6-month, and 1-year crude and adjusted mortality rates compared to the patients with a first STEMI, who enjoyed a highly significant decrease in crude mortality during the same period ( Table 3 ). However, the decrease only remained significant after adjustment for the 30-day mortality ( Table 4 ).
| Variable | 1998 | 2000 | 2002 | 2004 | 2006 | P Value for Trend | All | p Value Recurrent vs First |
|---|---|---|---|---|---|---|---|---|
| Recurrent STEMI (n) | 148 | 190 | 188 | 173 | 161 | 864 | ||
| In hospital | 11 (7.2%) | 17 (8.9%) | 15 (7.9%) | 14 (8.1%) | 13 (8.1%) | <0.92 | 70 (8.1%) | <0.0002 |
| At 30 days | 17 (11.5%) | 26 (13.7%) | 20 (10.6%) | 16 (9.2%) | 16 (10.0%) | <0.31 | 95 (11.1%) | <0.0007 |
| At 6 months | 27 (18.2%) | 32 (16.8%) | 25 (13.4%) | 23 (13.3%) | 25 (15.6%) | <0.33 | 132 (15.4%) | <0.0001 |
| At 1 year | 34 (23.0%) | 41 (21.6%) | 31 (16.7%) | 27 (15.6%) | 29 (18.1%) | <0.11 | 162 (18.9%) | <0.0001 |
| First STEMI (n) | 662 | 758 | 766 | 759 | 713 | 3,679 | ||
| In hospital | 34 (5.0%) | 56 (7.4%) | 34 (4.4%) | 31 (4.1%) | 24 (3.4%) | <0.008 | 179 (4.9%) | |
| At 30 days | 58 (8.8%) | 82 (10.8%) | 48 (6.3%) | 51 (6.7%) | 36 (5.1%) | <0.0002 | 275 (7.5%) | |
| At 6 months | 75 (11.3%) | 96 (12.7%) | 69 (9.0%) | 68 (9.0%) | 54 (7.6%) | <0.002 | 362 (9.9%) | |
| At 1 year | 80 (12.1%) | 108 (14.2%) | 73 (9.6%) | 77 (10.1%) | 60 (8.5%) | <0.002 | 398 (10.9%) |
| Variable | 1998 | 2000 | 2002 | 2004 | 2006 | p Value for Trend | All | p Value Recurrent vs First |
|---|---|---|---|---|---|---|---|---|
| Recurrent STEMI (n) | 152 | 190 | 188 | 173 | 161 | 864 | ||
| In hospital | 1.0 | 1.62 (0.64–4.11) | 1.34 (0.52–3.42) | 1.21 (0.46–3.18) | 1.12 (0.41–3.02) | <0.88 | 1.71 (1.19–2.44) | <0.004 |
| At 30 days | 1.0 | 1.63 (0.75–3.53) | 1.15 (0.52–2.58) | 0.86 (0.37–2.01) | 0.88 (0.37–2.12) | <0.32 | 1.47 (1.06–2.03) | <0.02 |
| At 6 months | 1.0 | 1.04 (0.53–2.03) | 0.83 (0.41–1.65) | 0.75 (0.36–1.55) | 0.88 (0.42–1.85) | <0.46 | 1.67 (1.25–2.22) | <0.0005 |
| At 1 year | 1.0 | 0.98 (0.53–1.81) | 0.74 (0.39–1.39) | 0.63 (0.32–1.22) | 0.72 (0.36–1.43 | <0.14 | 1.85 (1.41–2.43) | <0.0001 |
| First STEMI (n) | 684 | 758 | 766 | 759 | 712 | 3,679 | ||
| In hospital | 1.0 | 1.68 (1.02–2.77) | 1.06 (0.61–1.82) | 0.88 (0.51–1.51) | 1.04 (0.57–1.90) | <0.28 | 1.0 | |
| At 30 days | 1.0 | 1.46 (0.95–2.23) | 0.77 (0.48–1.23) | 0.77 (0.49–1.22) | 0.79 (0.48–1.32) | <0.03 | 1.0 | |
| At 6 months | 1.0 | 1.31 (0.89–1.93) | 0.88 (0.58–1.33) | 0.79 (0.53–1.19) | 0.92 (0.59–1.42) | <0.12 | 1.0 | |
| At 1 year | 1.0 | 1.46 (1.00–2.13) | 0.86 (0.57–1.28) | 0.87 (0.59–1.29) | 0.95 (0.62–1.45) | <0.13 | 1.0 |
| Variable | Crude Mortality Rate (%) | Adjusted Mortality | ||||
|---|---|---|---|---|---|---|
| 1998–2000 | 2002–2006 | p Value | 1998–2000 (OR) | 2002–2006 (HR; 95% CI) | p Value | |
| Recurrent MI (n) | 342 | 522 | ||||
| In hospital | 8.2 | 8.0 | <0.94 | 1.0 | 0.93 (0.51–1.69) | <0.82 |
| At 30 days | 12.7 | 10.0 | <0.21 | 1.0 | 0.73 (0.44–1.24) | <0.25 |
| At 6 months | 17.5 | 14.0 | <0.17 | 1.0 | 0.80 (0.51–1.26) | <0.33 |
| At 1 year | 22.2 | 16.8 | <0.05 | 1.0 | 0.70 (0.46–1.07) | <0.10 |
| First MI (n) | 1,942 | 2,237 | ||||
| In hospital | 6.2 | 4.0 | <0.0002 | 1.0 | 0.73 (0.52–1.03) | <0.07 |
| At 30 days | 9.9 | 6.0 | <0.0001 | 1.0 | 0.63 (0.47–0.85) | <0.002 |
| At 6 months | 12.0 | 8.6 | <0.0001 | 1.0 | 0.74 (0.57–0.96) | <0.02 |
| At 1 year | 13.2 | 9.4 | <0.0003 | 1.0 | 0.72 (0.56–0.93) | <0.01 |
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